ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.2398G>T (p.Val800Phe) (rs758697820)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521193 SCV000621673 uncertain significance not provided 2017-10-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYLK gene. The V800F variant has not been published as pathogenic or been reported as benign to our knowledge. The V800F variant is not observed in large population cohorts (Lek et al., 2016). The V800F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with TAAD (Stenson et al., 2014).
Invitae RCV000687502 SCV000815072 uncertain significance Aortic aneurysm, familial thoracic 7 2018-05-22 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 800 of the MYLK protein (p.Val800Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYLK-related disease. ClinVar contains an entry for this variant (Variation ID: 452832). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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